title: miR-155 inhibits oxidized low-density lipoprotein-induced apoptosis of RAW264.7 cells.
abstract: Macrophage apoptosis is a prominent feature of advanced atherosclerotic plaques. Here, we examined the hypothesis that the apoptotic machinery is regulated by microRNA-155 (miR-155). Constitutive expression of miR-155 was detected in RAW264.7 cells, which was increased following stimulation with oxidized low-density lipoprotein (OxLDL) in a dose- and time-dependent manner. OxLDL-treated RAW264.7 cells showed a marked time- and dose-dependent increase in apoptosis, which was suppressed in the presence of mimics and increased with antagonists of miR-155. Bioinformatics analysis revealed Fas-associated death domain-containing protein (FADD) as a putative target of miR-155. Luciferase reporter assay and Western blot further disclosed that miR-155 inhibits FADD expression by directly targeting the 3'-UTR region. We propose that miR-155 attenuates the macrophage apoptosis, at least in part, through FADD regulation, since forced expression of FADD blocked the ability of miR-155 to inhibit apoptosis. Our results collectively suggest that miR-155 attenuates apoptosis of OxLDL-mediated RAW264.7 cells by targeting FADD, supporting a possible therapeutic role in atherosclerosis.
authors.forename: Guo-fu
authors.initials: GF
authors.lastname: Zhu
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Yang
authors.forename: Rui-wei
authors.initials: RW
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yan-kun
authors.initials: YK
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Jin-shan
authors.initials: JS
authors.lastname: Ye
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Liang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D053200:Fas-Associated Death Domain Protein; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein